Little is known about the organization and expression of the mitochondrial genome of Plasmodium falciparum, a causative agent of human malaria. Asexual erythrocytic stages rely on glycolysis for energy production but insect stages of the life cycle may have a fully functional mitochondrial respiratory system. This is reminiscent of the differential expression of the mitochondrial respiratory system during the life cycle of Trypanosoma brucei, which involves coordination of multiple mechanisms at the transcript level. This proposal is designed to investigate the organization and expression of the mitochondrial genome and to assess the potential for differential expression of mitochondrial genes during the life cycle. P. falciparum mitochondrial DNA will be isolated, cloned, and mapped. Specific genes will be identified and their structural organization, including nucleotide sequence, will be determined. Initial studies will concentrate on the genes for apocytochrome b, which may be differentially expressed, and cytochrome c oxidase I and the mitochondrial rRNAs, which are likely to be expressed in all life cycle stages. The general characteristics of the transcripts of specific mitochondrial genes will be investigated and transcripts will be compared between erythrocytic stages, including gametocytes to examine potential differential expression. These experiments will contribute to assessing the role of the mitochondrial genome during the life cycle of P. falciparum. In addition, the antimalarial action of many compounds which affect mitochondrial function suggests that these studies may provide insights into new chemotherapeutic approaches to the treatment of malaria.